CXCL16 participates in pathogenesis of immunological liver injury by regulating T lymphocyte infiltration in liver tissue

AIM： To investigate the role of CXCL16 in the pathogenesis of immunological liver injury and to explore the possible mechanism ofT lymphocyte infiltration regulated by CXCL16. METHODS： Immunological liver injury in murine model was induced by Bacille Calmette-Guerin and lipopolysaccharide. Expression pattern and distribution of CXCL16 were examined by real-time quantitative RT-PCR and immunohistochemical analysis. Anti-CXCL16 antibody was administrated in vivo to investigate its effect on T-cell recruitment and acute hepatic necrosis. The survival of murine model was also evaluated. RESULTS, The murine immunological liver injury model was successfully established, CXCL16 expression increased and predominantly distributed in periportal areas and vascular endothelia in injured liver tissues. Administration of anti-CXCL16 Ab protected the mice from death and acute liver damage. Approximately 70% of the mice survived for 72 h in the anti-CXCL16 Ab treatment group, whereas 80% died within 72 h in control Ab group. The number of liver-infiltrating T lymphocytes was significantly reduced from 1.01×10^7 to 3.52×10^6/liver, compared with control Ab treatment. CONCLUSION： CXCL16 is involved in immunological liver injury by regulating T lymphocyte infiltration in liver tissue.

Study on Protection Mechanism of Viscum coloratum (Kom.) Nakai f. lutescens kitag Fruit Polysaccharides on Mice with Acute Alcoholic Liver Injury

This study was conducted to investigate the protective mechanism of V. coloratum fruit polysaccharides（ VCFP） on mice with acute alcoholic liver injury. Acute liver injury model was built by one-time alcohol gavage. The mice were randomly divided into VCFP-treated groups（ low-,medium-,and highdose）,alcohol model group and normal control group at the same time. VCFP-treated groups were administrated polysaccharide intragastrically continuously for4 weeks; and the alcohol model group and normal control group were administrated intragastrically the same amount of normal saline. The general situation and liver tissue morphological structure changes were observed. The results showed that the levels of ALT,AST,TC,TG,MDA contents,and CAT and GSH-Px activity of mice in the model group increased significantly（ P 〈 0. 01）,while the activity of SOD and weight and liver index decreased significantly（ P 〈 0. 01） compared with the normal control group. After 4 weeks of gavage,VCFP could significantly improve weight,liver index and SOD activity,and significantly reduce ALT,AST,TC and TG levels,MDA content and CAT and GSH-Px activity. These results suggest that VCFP can improve antioxidant enzyme activity,remove oxygen free radical and reduce membrane lipid peroxidation reaction,thereby protecting liver cells.

Prediction of the mechanisms of liver injury of Epimedii Folium by network pharmacology and validation in HepaRG Cells

Objective:EpimediiFolium(EF),a traditional Chinese medicinal material,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism.However,its clinical applications are limited by its drug-induced liver injury(DILI)effects and the underlying mechanisms have not been elucidated.Methods:Active EF compounds were obtained from the TCMSP database and their targets predicted in Targetnet.Next,DILI-targets were obtained from CTD,Genecards and Digsee databases.Protein-protein interactions of EF DILI-targets were determined using STRING and hub targets identified via topological analyses.Then,hub targets were subjected to GO and KEGG pathway enrichment analyses.Finally,HepaRG cells were used for further validation of molecular mechanisms.Results:Fifty seven active compounds and 164 targets that interacted with these active compounds were identified with Sagittatoside A,icariside I,and Icariin being the best active compounds.Enrichment analysis revealed the PI3K/Akt and NF-kB signaling pathways to be markedly enriched.Molecular docking revealed that Sagittatoside A,icariside I and Icariin had good binding activities to RAC1,PTGS2,and NOS3.Validation analysis in HepaRG cells revealed that Epimedium flavonoids upregulated RAC1,PTGS2 and NOS3 levels.Conclusion:Our findings show that EF induces oxidative stress,inflammation,and apoptosis via PI3K/Akt and NF-kB signaling pathways,and provides a basis for more in-depth studies on EF-induced DILI.

Study on Intervenient Effect of Angelica Sinensis Polysaccharide on Immunological Liver Injury and Its Mechanism in Mice

Objective: To study the changes of expressions of nitric oxide synthase (NOS) of the constitutive type (cNOS) and inducible type (iNOS), the apoptosis related genes bax and bcl 2, as well as the tumor necrosis factor (TNF α) in immunological liver injury (ILI) and to explore the preventive effects of Angelica sinensis polysaccharide (ASP) on ILI and its mechanism in mice.Methods: ILI model mice induced by intraperitoneal injection of lipo polysaccharide (LPS) and BCG vaccine were treated with ASP of different doses (30mg/kg, 60mg/kg) by gastrogavage every day for 7 days. The serum alanine transaminase (ALT) and glutathione S transferase (GST) activities and NO content in the liver were detected; the expressions of cNOS, iNOS, bcl 2, bax were assessed with immuno histochemical method, and the TNF α mRNA expression in the liver was observed by reverse transcriptase polymerase chain reaction (RT PCR).Results: Compared with the normal mice , the NO production and ALT, GST levels were raised significantly in the model mice, the TNF α mRNA expression was also raised significantly. But no obvious changes of cNOS was found. Small dose ASP (30mg/kg) could reduce NO production and ALT, GST levels in model mice by 19.5%, 23.7% and 40.0% respectively, decrease the expression of iNOS and bax by 48.3%, and 26.4%, and increase the expression of cNOS, bcl 2 by 66.9% and 337.3%, respectively, but it could not reduce the TNF α mRNA expression in the liver. Large dose of ASP (60mg/kg) was not more effective than that of small dose.Conclusion: Changes of NO production and TNF α mRNA may play an important role in ILI. The mechanism of ASP in intervening ILI may be through modulation on cNOS, iNOS, bax, bcl 2 expression to block the damage of BCG vaccine and LPS on hepatocytes.

Study on the Protective Effect and Mechanism of Tibetan Medicine Ershiwuwei Songshi Pill on Acute Alcoholic Liver Injury in Rats

[Objectives]To investigate the protective effect and mechanism of Ershiwuwei Songshi Pill on acute alcoholic liver injury in rats.[Methods]Sixty male SD rats were randomly divided into normal control group,model group,polyene phosphatidylcholine(82.08 mg/kg)positive control group and Ershiwuwei Songshi Pill high(180 mg/kg),medium(90 mg/kg)and low(45 mg/kg)dose groups.The rats in each group were given corresponding drugs by intragastric administration for 3 d and fed normally.From the 4th d,all groups except the normal control group were fed with 15 mL/kg liquor(56%vol)for 7 d after 2 h of administration.After the last modeling,the levels of AST,ALT,TC,TG,SOD,GSH in serum and IL-1β,IL-6,TNF-αin liver tissue were measured.The protein expressions of Bax,Bcl-2 and Caspase3 were determined by Western blotting.HE staining was used to observe the pathological changes of liver tissue under light microscope.[Results]Compared with the model group,the body weight and the levels of SOD and GSH in the treatment group were significantly higher than those in the model group;liver index,serum ALT,AST,TC,TG,IL-1β,IL-6 and TNF-αlevels decreased significantly(P<0.01 or P<0.05);HE staining showed that there was a small amount of collagen proliferation and lymphocyte infiltration in connective tissue around the hepatic portal area in the model group,multiple inflammatory foci could be seen in the lobules,and round fat vacuoles could be seen in the cytoplasm;in each administration group,the pathological condition of the liver was mild.[Conclusions]Ershiwuwei Songshi Pill had a certain protective effect on acute alcoholic liver injury in rats,and its mechanism might be related to reducing enzyme,promoting lipid metabolism and anti-inflammation.

Exploration on the mechanism of therapeutic and toxic bidirectional effects of Haizao Yuhu decoction based on machine learning and data mining

Objective:To explore the bidirectional mechanism of Haizao Yuhu decoction(HYD)on goiter and drug-induced liver injury(DILI)based on machine learning and data mining.Methods:Firstly,compounds of HYD were selected from the TCMSP,TCMIP,and BATMAN databases,then the TCMSP was used to acquire the targets of compounds.Targets of goiter and DILI were obtained from the GeneCards database.Secondly,common targets of“HYD-goiter”and“HYD-DILI”as well as related compounds were used to construct the networks and perform Random Walk with Restart(RWR)algorithm and network stability test.Finally,core targets in the“HYD-goiter”and“HYD-DILI”networks were used for molecular docking with core compounds and searched for validation on PubChem,and the relevant experimental data of our group were quoted to verify the analysis results.Results:There were 22 intersection targets of HYD and DILI,326 of HYD and goiter.RWR analysis showed that MAPK1,MAPK3,AKT1,etc.may be the core targets of HYD treating goiter,RELA,TNF,IL4,etc.may be the core targets of the bidirectional effect,and eckol may be the core compound in bidirectional effect.Network stability test indicated that the HYD had a high stability on treating goiter and playing a bidirectional effect.The core targets and core compounds docked well,and 37.3%of targets had been confirmed by experiments and 29.8%core targets had been confirmed.Our previous experimental result confirmed that the HYD could treat goiter usefully by reducing the expression levels of PI3K and AKT mRNA,and down-regulating the expression of Cyclin D1 and Bcl-2 mRNA.Conclusion:HYD containing“sargassum-liquorice”combination may have a bidirectional effect on treating goiter and causing DILI.We offered a new way for more explorations on the therapeutic and toxic bidirectional mechanisms based on machine learning and data mining.

Hepatic ischemia-reperfusion injury in liver transplant setting:mechanisms and protective strategies

Hepatic ischemia-reperfusion injury is a major cause of liver transplant failure,and is of increasing significance due to increased use of expanded criteria livers for transplantation.This review summarizes the mechanisms and protective strategies for hepatic ischemia-reperfusion injury in the context of liver transplantation.Pharmacological therapies,the use of pre-and post-conditioning and machine perfusion are discussed as protective strategies.The use of machine perfusion offers significant potential in the reconditioning of liver grafts and the prevention of hepatic ischemia-reperfusion injury,and is an exciting and active area of research,which needs more study clinically.

Characteristics and Mechanism of Liver Injury in 2019 Coronavirus Disease

An outbreak of severe acute respiratory syndrome coronavi-rus 2(SARS-CoV-2)infection(2019 coronavirus disease,COVID-19)since December 2019,from Wuhan,China,has been posing a significant threat to global human health.The clinical features and outcomes of Chinese patients with COVID-19 have been widely reported.Increasing evidence has witnessed the frequent incident liver injury in COVID-19 patients,and it is often manifested as transient elevation of serum aminotransferases;however,the patients seldom have liver failure and obvious intrahepatic cholestasis,unless pre-existing advanced liver disease was present.The underlying mechanisms of liver injury in cases of COVID-19 might include psychological stress,systemic inflammation re-sponse,drug toxicity,and progression of pre-existing liver diseases.However,there is insufficient evidence for SARS-CoV-2 infected hepatocytes or virus-related liver injury in COVID-19 at present.The clinical,pathological and labora-tory characteristics as well as underlying pathophysiology and etiology of liver injury in COVID-19 remain largely unclear.In this review,we highlight these important issues based on the recent developments in the field,for optimizing the manage-ment and treatment of liver injury in Chinese patients with COVID-19.

Impact of non-alcoholic fatty liver disease on coronavirus disease 2019: A systematic review

BACKGROUND Many studies have revealed a link between non-alcoholic fatty liver disease(NA-FLD)and coronavirus disease 2019(COVID-19),making understanding the relationship between these two conditions an absolute requirement.AIM To provide a qualitative synthesis on the currently present data evaluating COVID-19 and NAFLD.METHODS This systematic review was conducted in accordance with the guidelines pro-vided by preferred reporting items for systematic reviews and meta-analyses and the questionnaire utilized the population,intervention,comparison,and outcome framework.The search strategy was run on three separate databases,PubMed/MEDLINE,Scopus,and Cochrane Central,which were systematically searched from inception until March 2024 to select all relevant studies.In addition,ClinicalTrials.gov,Medrxiv.org,and Google Scholar were searched to identify grey literature.RESULTS After retrieval of 11 studies,a total of 39282 patients data were pooled.Mortality was found in 11.5%and 9.4%of people in NAFLD and non-NAFLD groups.In all,23.2%of NAFLD patients and 22%of non-NAFLD admissions diagnosed with COVID-19 were admitted to the intensive care unit,with days of stay varying.Ventilatory support ranged from 5%to 40.5%in the NAFLD cohort and from 3.1%to 20%in the non-NAFLD cohort.The incidence of acute liver injury showed significance.Clinical improvement on days 7 and 14 between the two classifications was significant.Hospitalization stay ranged from 9.6 days to 18.8 days and 7.3 days to 16.4 days in the aforementioned cohorts respectively,with 73.3%and 76.3%of patients being discharged.Readmission rates varied.CONCLUSION Clinical outcomes except mortality consistently showed a worsening trend in patients with NAFLD and concomitant COVID-19.Further research in conducting prospective longitudinal studies is essential for a more powerful conclusion.

Liver injury in COVID-19:Detection,pathogenesis,and treatment

In the early December 2019,a novel coronavirus named severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan,China,followed by an outbreak that spread around the world.Numerous studies have shown that liver injury is common in patients with coronavirus disease 2019(COVID-19),and may aggravate the severity of the disease.However,the exact cause and specific mechanism of COVID-associated liver injury needs to be elucidated further.In this review,we present an analysis of the clinical features,potential mechanisms,and treatment strategies for liver injury associated with COVID-19.We hope that this review would benefit clinicians in devising better strategies for management of such patients.

Acute liver injury in COVID-19 patients hospitalized in the intensive care unit:Narrative review

In recent years,humanity has been confronted with a global pandemic due to coronavirus disease 2019(COVID-19),which has caused an unprecedented health and economic crisis worldwide.Apart from the respiratory symptoms,which are considered the principal manifestations of COVID-19,it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems.Across the spectrum of organ involvement in COVID-19,acute liver injury(ALI)has been gradually gaining increasing attention by the international scientific community.COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course.Indeed,COVID-19 patients hospitalized in the intensive care unit(ICU)run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure.The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature.Several theories have been proposed to explain the occurrence of ALI in the ICU setting,such as hypoperfusion and ischemia due to hemodynamic instability,passive liver congestion as a result of congestive heart failure,ischemia-reperfusion injury,hypoxia due to respiratory failure,mechanical ventilation itself,sepsis and septic shock,cytokine storm,endotheliitis with concomitant coagulopathy,druginduced liver injury,parenteral nutrition and direct cytopathic viral effect.It should be noted that no specific therapy for COVID-19 induced ALI exists.Therefore,the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues.The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients,explore its clinical implications,shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches.Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues,in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.

Therapeutic plasma exchange and a double plasma molecular absorption system in the treatment of thyroid storm with severe liver injury: A case report

BACKGROUND Thyroid storm is resistant to conventional treatments including antithyroid drugs and 131I therapeutic means.Plasma exchange(PE)and double plasma molecular absorption system(DPMAS)can be used as an effective treatment for thyroid storm with severe liver injury.CASE SUMMARY A 52-year-old woman presented with a 10-day history of nausea and vomiting accompanied by yellowing of the skin and mucosa.Further,her free T3(FT3)and FT4 levels were significantly elevated,whereas her thyrotropin level was reduced.After admission,her condition continued to deteriorate,and she presented with continued high fever,vomiting,palpitation,and shortness of breath.After being diagnosed with thyroid storm,the patient was immediately treated with PE combined with DPMAS.Her symptoms improved immediately.After three PE+DPMAS treatments,and she was discharged from the hospital.She was treated with methylprednisolone and methylthimidazole.After six months,the patient spontaneously discontinued methylthimidazole treatment.Her previous clinical manifestations and liver dysfunction reoccurred.The patient was treated with PE+DPMAS two times,and her condition rapidly improved.Liver histopathology indicated immunological liver injury.CONCLUSION Our experience suggests that PE combined with DPMAS can effectively relieve the development of thyroid storm.

Liver injury induced by COVID 19 treatment–what do we know?

The severity of coronavirus disease 2019(COVID-19)may be correlated with the risk of liver injury development.An increasing number of studies indicate that degrees of hepatotoxicity have been associated with using some medications in the management of COVID-19 patients.However,limited studies have systematically investigated the evidence of drug-induced liver injury(DILI)in COVID-19 patients.An increasing number of studies indicate that degrees of hepatotoxicity have been associated with using some of these medications in the management of COVID-19 patients.Significantly,it was relieved after the cessation of these agents.However,to our knowledge,no studies have systematically investigated the evidence of DILI in COVID-19 patients.In this review,we discussed the association between hepatotoxicity in COVID-19 patients and the drugs used in these patients and possible mechanisms of hepatotoxicity.The currently available evidence on the association of different therapeutic agents with hepatotoxicity in COVID-19 patient was systematically reviewed.

基于网络药理学探讨葛根治疗肝损伤的作用机制

目的:探究葛根治疗肝损伤的有效成分、靶标和作用通路,为葛根用于肝损伤的治疗提供理论依据。方法:基于中医药整合药理学网络计算平台(TCMIP)、中药综合资源数据库(TCMID)、中药系统药理数据库和分析平台(TCMSP)、人类基因数据库(GeneCards)等公共数据库和KEGG通路分析等网络药理学基本方法预测葛根治疗肝损伤的作用机制。结果:葛根主要活性成分靶点与肝损伤靶点具有交集,功能分析、富集分析和分子对接发现,刺芒柄花素、β-谷甾醇与雌激素受体1(ESR1),香豆雌酚、3′-甲氧基大豆黄素与PPARG与之间对接具有良好的亲和力,其中刺芒柄花素与ESR1之间作用力最强(-8.04 kcal/mol)。推断葛根治疗肝损伤的机制与ESR1和PPARG介导的路径相关。结论:葛根治疗肝损伤可能通过ESR信号通路、PPAR-γ激活和调节靶基因转录等发挥调节肝细胞的生长、分化和生理功能,减轻氧化应激性肝损伤和肝细胞凋亡的作用。

Epigenetics of proteasome inhibition in the liver of rats fed ethanol chronically

AIM： TO examine the effects of ethanol-induced proteasome inhibition, and the effects of proteasome inhibition in the regulation of epigenetic mechanisms.METHODS： Rats were fed ethanol for 1 mo using the Tsukamoto-French model and were compared to rats given the proteasome inhibitor PS-341 （Bortezomib, Velcade^TM） by intraperitoneal injection. Microarray analysis and real time PCR were performed and proteasome activity assays and Western blot analysis were performed using isolated nuclei.RESULTS： Chronic ethanol feeding caused a significant inhibition of the ubiquitin proteasome pathway in the nucleus, which led to changes in the turnover of transcriptional factors, histone-modifying enzymes, and, therefore, affected epigenetic mechanisms. Chronic ethanol feeding was related to an increase in histone acetylation, and it is hypothesized that the proteasome proteolytic activity regulated histone modifications by controlling the stability of histone modifying enzymes, and, therefore, regulated the chromatin structure, allowing easy access to chromatin by RNA polymerase, and, thus, proper gene expression. Proteasome inhibition by PS-341 increased histone acetylation similar to chronic ethanol feeding. In addition, proteasome inhibition caused dramatic changes in hepatic remethylation reactions as there was a significant decrease in the enzymes responsible for the regeneration of S-adenosylmethionine, and, in particular, a significant decrease in the betaine-homocysteine methyltransferase enzyme. This suggested that hypomethylation was associated with proteasome inhibition, as indicated by the decrease in histone methylation.CONCLUSION： The role of proteasome inhibition in regulating epigenetic mechanisms, and its link to liver injury in alcoholic liver disease, is thus a promising approach to study liver injury due to chronic ethanol consumption.

中药调节肠道菌群缓解药物性肝损伤的研究进展

药物性肝损伤是由化学药物、膳食补充剂和草药产品等引起的肝脏损伤疾病,其极易发展为肝衰竭,且在其发生发展的同时常伴随肠道菌群的变化。中药多成分、多靶点的治疗特点可以通过调节肠道菌群、改善肠道屏障、降低炎症因子水平等减轻药物性肝损伤。对中药干预肠道菌群缓解药物性肝损伤的作用进行总结,以期对中药治疗药物性肝损伤的机制研究提供参考。

中性粒细胞在药物性肝损伤中的作用研究进展

在药物性肝损伤(DILI)的疾病发展过程中,被募集到肝脏中的中性粒细胞通过多种途径加重肝损伤的作用受到广泛关注。然而,中性粒细胞在不同种类药物导致的直接型、间接型、特异质型DILI中的作用机制不同,尚待进一步研究。综述中性粒细胞在DILI中发挥加重肝损伤作用以及中性粒细胞分别在乙酰氨基酚、雷公藤甲素和吡咯里西啶生物碱导致的直接型DILI,氟烷诱导的特异质型DILI,免疫检查点抑制剂引起的间接型DILI中的作用机制,为探究DILI的内在机制和治疗手段提供参考。

Nuclear effects of ethanol-induced proteasome inhibition in liver cells

Alcohol ingestion causes alteration in several cellular mechanisms, and leads to inflammation, apoptosis, immunological response defects, and fibrosis. These phenomena are associated with significant changes in the epigenetic mechanisms, and subsequently, to liver cell memory. The ubiquitin-proteasome pathway is one of the vital pathways in the cell that becomes dysfunctionial as a result of chronic ethanol consumption. Inhibition of the proteasome activity in the nucleus causes changes in the turnover of transcriptional factors, histone modifying enzymes, and therefore, affects epigenetic mechanisms. Alcohol consumption has been associated with an increase in histone acetylation and a decrease in histone methylation, which leads to gene expression changes. DNA and histone modifications that result from ethanol-induced proteasome inhibition are key players in regulating gene expression, especially genes involved in the cell cycle, immunological responses, and metabolism of ethanol. The present review highlights the consequences of ethanol-induced proteasome inhibition in the nucleus of liver cells that are chronically exposed to ethanol.

基于网络药理学探究苦苣菜治疗急性肝损伤的作用机制

目的 基于网络药理学及多种中药、基因数据库综合分析苦苣菜治疗急性肝损伤的作用机制。方法 通过超高效液相色谱-质谱数据、TCMSP及HERB获取苦苣菜主要活性成分,借助Swiss Target Prediction获取活性成分潜在靶点;使用Cytoscape3.9.1构建苦苣菜活性成分-靶点网络;通过Genecard、OMIM获取急性肝损伤靶点;利用微生信平台获取药物与疾病共同靶点并制作Venn图;运用STRING构建PPI网络并筛选核心靶点;利用DAVID进行GO、KEGG富集分析,利用微生信平台、Adobe Illustrator 2022对结果可视化分析。结果 从苦苣菜中筛选出21种活性成分,其相关靶点与急性肝损伤靶点相交集85个靶点,最终获得22个关键靶点;主要富集于338条生物学过程、51条细胞组成、103条分子功能,调控131条急性肝损伤相关信号通路。结论 苦苣菜可能通过TNF、TP53等关键靶点调控癌症等信号通路,为研究苦苣菜治疗急性肝损伤及后续新药研发提供依据。

基于网络药理学的何首乌致肝损伤作用机制研究

目的:通过网络药理学的技术和方法,筛选何首乌相关化学成分映射肝损伤作用靶点,构建何首乌成分-靶点-肝损伤网络图,探讨何首乌致肝损伤的作用机制。方法:通过TCMID、TCMGenDIT数据库及综合已报道文献检索何首乌化学成分,从中药系统药理学分析平台(TCMSP)、BATMAN-TCM数据库筛选并获取成分对应靶点;通过DrugBank、DisGeNET、GeneCards多数据库联合检索肝损伤靶点,整合分析交集靶点建立STRING蛋白交互关系,利用Cytoscape 3.7.1软件构建成分-靶点-肝损伤可视化网络;通过DAVID数据库对交集靶点基因功能(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果:共筛选收集何首乌化学成分38个,成分靶点307个,肝损伤靶点6140个,成分与肝损伤交集靶点252个,GO生物功能富集分析共涉及838个,KEGG通路富集分析为111条,预测其涉及肝损伤作用机制通路主要包括cAMP信号通路、MAPK信号通路、非酒精性脂肪性肝病(NAFLD)、HIF-1信号通路、药物代谢-细胞色素P450、TNF信号通路、PI3K-Akt信号通路、NOD样受体信号通路、Toll样受体信号通路、Wnt信号通路。结论:进一步阐释了何首乌多成分、多靶点、多通路共同作用的特点,为解析何首乌致肝损伤作用机制研究提供新思路和新方向。